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排序方式: 共有341条查询结果,搜索用时 15 毫秒
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He Li Lawrence M Schopfer Florian Nachon Marie-Thérèse Froment Patrick Masson Oksana Lockridge 《Toxicological sciences》2007,100(1):136-145
Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage. 相似文献
3.
Seyrantepe V Poupetova H Froissart R Zabot MT Maire I Pshezhetsky AV 《Human mutation》2003,22(5):343-352
Lysosomal sialidase (EC 3.2.1.18) has a dual physiological function; it participates in intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in the sialidase gene NEU1, located on chromosome 6p21.3, result in autosomal recessive disorder, sialidosis, which is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. Sialidosis type I is a milder, late-onset, normosomatic form of the disorder. Type I patients develop visual defects, myoclonus syndrome, cherry-red macular spots, ataxia, hyperreflexia, and seizures. The severe early-onset form, sialidosis type II, is also associated with dysostosis multiplex, Hurler-like phenotype, mental retardation, and hepatosplenomegaly. We summarize information on the 34 unique mutations determined so far in the sialidase gene, including four novel missense and one novel nonsense mutations found in two Czech and two French sialidosis patients. The analysis of sialidase mutations in sialidosis revealed considerable molecular heterogeneity, reflecting the diversity of clinical phenotypes that make molecular diagnosis difficult. The majority of sialidosis patients have had missense mutations, many of which have been expressed; their effects on activity, stability, intracellular localization, and supramolecular organization of sialidase were studied. A structural model of sialidase allowed us to localize mutations in the sialidase molecule and to predict their impact on the tertiary structure and biochemical properties of the enzyme. 相似文献
4.
Nguyen Khac F Waill MC Romana SP Radford-Weiss I Busson M Collonge-Rame MA Ribadeau-Dumas A Piffaut MC Daniel MT Davi F Merle-Béral H Berger R Arock M 《Cancer Genetics and Cytogenetics》2002,138(1):22-26
Two patients with Ph-positive chronic myelocytic leukemia in erythroblastic transformation and rearrangement of the short arm of chromosome 18 are reported. Fluorescence in situ hybridization studies showed that the 18p rearrangement resulted from translocation of the main part of chromosome 22 long arm to 18p, including BCR-ABL1 fusion. The 18p abnormality resulted, thus, in loss of 18p and duplication of BCR-ABL1 in both patients. The possible relation to the erythroblastic type of blastic phase is briefly discussed. In addition an apparently intact germline ABL1 gene was duplicated and inserted into chromosome 6 at band p21 in one of these patients. 相似文献
5.
Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. 总被引:9,自引:0,他引:9
Emmanuel Raffoux Philippe Rousselot J?el Poupon Marie-Thérèse Daniel Bruno Cassinat Richard Delarue Anne-Laure Taksin Delphine Réa Agnès Buzyn Annick Tibi Geneviève Lebbé Patricia Cimerman Christine Chomienne Jean-Paul Fermand Hugues de Thé Laurent Degos Olivier Hermine Hervé Dombret 《Journal of clinical oncology》2003,21(12):2326-2334
PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested. 相似文献
6.
Frémeaux-Bacchi V Guinnepain MT Cacoub P Dragon-Durey MA Mouthon L Blouin J Cherin P Laurent J Piette JC Fridman WH Weiss L Kazatchkine MO 《The American journal of medicine》2002,113(3):194-199
PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder. 相似文献
7.
Mona Momeni Cécile Carlier Philippe Baele Christine Watremez Michel Van Dyck Amine Matta David Kahn Marie-Thérèse Rennotte David Glineur Laurent de Kerchove Luc-Marie Jacquet Dominique Thiry André Grégoire Stéphane Eeckhoudt Cédric Hermans 《Journal of cardiothoracic and vascular anesthesia》2013,27(1):5-11
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9.
Complement receptor 2 (CR2) and its physiological ligand, C3d, known for its molecular adjuvant property on the immune response, exhibit opposite effects with regard to autoimmunity. Although CR2 has been implicated in maintaining self-tolerance, recent studies reported a role for C3d signaling to CR2 in tolerance breakdown to self-antigens and the initiation of inflammatory autoimmune pathologies. In the present study, we have investigated the effect of C3d in a model of tolerogenic DNA vaccination encoding the myelin oligodendrocyte glycoprotein (MOG-DNA) which protected mice from the induction of an experimental autoimmune encephalomyelitis (EAE). We show that fusing two or three copies of C3d to MOG overcomes the protective effect of DNA vaccination. Multimeric C3d was able to revert the unresponsiveness state of specific T cells induced by MOG-DNA, independently of a modification in the Th1/Th2 cytokine pattern. Interestingly, the adjuvant effect of C3d was not sufficient to boost the anti-MOG antibody response after DNA vaccination. These findings suggest that C3d might be involved in self-tolerance breakdown and could contribute to the pathogenesis of central nervous system autoimmune disorders. 相似文献
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